The studies are designed to examine the existence of mechanisms by which hyperglycemia and/or insulin deficiency may induce alterations in the metabolism and structure of aortic intima-media and peripheral nerve which could contribute to the development of specific lesions affecting these tissues in chronic diabetes mellitus. The metabolism of a newly described aortic intima-media preparation containing an intact endothelium will be characterized. The effects of elevated glucose concentrations on the metabolism, composition, and fine structure of rabbit aortic intima-media will be examined, as will the relationship of alterations in the activity of the polyol pathway, and in the metabolism of free myoinositol (MI) and scyllo-inositol to alterations induced by high glucose concentrations. The relationship of hyperglycemia to the development of impaired peripheral motor nerve conduction velocity (MNCV) in acute streptozotocin diabetes in rats will be determined; studies of the relationship of alterations in the metabolism of free MI, scyllo-inositol, and inositol containing phospholipids to the development of impaired MNCV will be extended. An effort will be made to develop a model for overt diabetic polyneuropathy in rats with chronic streptozotocin diabetes. The factors responsible for the maintenance of high tissue/plasma free MI concentrations in various rat tissues will be examined, as will the alterations associated with experimental diabetes and the signficance of dietary free MI in diabetes. The sources of plasma free MI and scyllo-inositol, and the factors affecting tissue scyllo-inositol concentrations will be determined.